ArticleThe Journal of experimental medicine2009
Pre-B cell receptor-mediated cell cycle arrest in Philadelphia chromosome-positive acute lymphoblastic leukemia requires IKAROS function.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 126 citations in OpenAlex.
- IKAROS deletions dictate a unique gene expression signature in patients with adult B-cell acute lymphoblastic leukemia.PloS one · 2012Trial
- IKAROS isoforms differentially control gene expression and differentiation of a B-cell acute lymphoblastic leukemia cell line.Nagoya journal of medical science · 2026Article
- An antibody-drug conjugate targeting VpreB1 for the treatment of B-cell acute lymphoblastic leukemia.Blood neoplasia · 2025Article
- Glucocorticoids paradoxically promote steroid resistance in B cell acute lymphoblastic leukemia through CXCR4/PLC signaling.Nature communications · 2024Article
- Niche-expressed Galectin-1 is involved in pre-B acute lymphoblastic leukemia relapse through pre-B cell receptor activation.iScience · 2023Article
- IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?International journal of molecular sciences · 2023Review
- Article
- Galectin-1 and Galectin-3 in B-Cell Precursor Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2022Article
- Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia.Epigenomes · 2022Article
- Genetic Biomarkers and Their Clinical Implications in B-Cell Acute Lymphoblastic Leukemia in Children.International journal of molecular sciences · 2022Review
- VpreB surrogate light chain expression in B-lineage ALL: a report from the Children's Oncology Group.Blood advances · 2022Article
- C/EBPβ induces B-cell acute lymphoblastic leukemia and cooperates with BLNK mutations.Cancer science · 2021Article
- Article
- It Takes Three Receptors to Raise a B Cell.Trends in immunology · 2020Review
- Long-read sequencing unveils IGH-DUX4 translocation into the silenced IGH allele in B-cell acute lymphoblastic leukemia.Nature communications · 2019Article
- Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation.Nature reviews. Immunology · 2019Review
- Article
- Continuous signaling of CD79b and CD19 is required for the fitness of Burkitt lymphoma B cells.The EMBO journal · 2018Article
- Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse.Nature medicine · 2018Article
- The many faces of IKZF1 in B-cell precursor acute lymphoblastic leukemia.Haematologica · 2018Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 9 institutions in 4 countries.
Funding
Abstract
B cell lineage acute lymphoblastic leukemia (ALL) arises in virtually all cases from B cell precursors that are arrested at pre-B cell receptor-dependent stages. The Philadelphia chromosome-positive (Ph(+)) subtype of ALL accounts for 25-30% of cases of adult ALL, has the most unfavorable clinical outcome among all ALL subtypes and is defined by the oncogenic BCR-ABL1 kinase and deletions of the IKAROS gene in >80% of cases. Here, we demonstrate that the pre-B cell receptor functions as a tumor suppressor upstream of IKAROS through induction of cell cycle arrest in Ph(+) ALL cells. Pre-B cell receptor-mediated cell cycle arrest in Ph(+) ALL cells critically depends on IKAROS function, and is reversed by coexpression of the dominant-negative IKAROS splice variant IK6. IKAROS also promotes tumor suppression through cooperation with downstream molecules of the pre-B cell receptor signaling pathway, even if expression of the pre-B cell receptor itself is compromised. In this case, IKAROS redirects oncogenic BCR-ABL1 tyrosine kinase signaling from SRC kinase-activation to SLP65, which functions as a critical tumor suppressor downstream of the pre-B cell receptor. These findings provide a rationale for the surprisingly high frequency of IKAROS deletions in Ph(+) ALL and identify IKAROS-mediated cell cycle exit as the endpoint of an emerging pathway of pre-B cell receptor-mediated tumor suppression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.